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This study uses pooled analysis to explore the in-depth effects of pemafibrate, a selective peroxisome proliferator-activated receptor \u03b1 modulator (SPPARM\u03b1) already known to decrease elevated triglycerides, on glucose metabolism and liver function in patients with hypertriglyceridemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a post-hoc analysis of six phase 2 and phase 3 Japanese randomized double-blind placebo-controlled trials that examined the effects of daily pemafibrate 0.1\u2009mg, 0.2\u2009mg, and 0.4\u2009mg on glucose metabolism markers and liver function tests (LFTs). Primary endpoints were changes in glucose metabolism markers and LFTs from baseline after 12\u2009weeks of pemafibrate treatment. All adverse events and adverse drug reactions were recorded as safety endpoints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study population was 1253 patients randomized to placebo (n\u2009=\u2009298) or pemafibrate 0.1\u2009mg\/day (n\u2009=\u2009127), 0.2\u2009mg\/day (n\u2009=\u2009584), or 0.4\u2009mg\/day (n\u2009=\u2009244). Participant mean age was 54.3\u2009years, 65.4\u2009% had BMI\u2009\u2265\u200925\u2009kg\/m<jats:sup>2<\/jats:sup>, 35.8\u2009% had type 2 diabetes, and 42.6\u2009% had fatty liver. Fasting glucose, fasting insulin, and HOMA-IR decreased significantly in all pemafibrate groups compared to placebo. The greatest decrease was for pemafibrate 0.4\u2009mg\/day: least square (LS) mean change from baseline in fasting glucose \u2212\u20090.25\u2009mmol\/L; fasting insulin \u2212\u20093.31 \u00b5U\/mL; HOMA-IR \u2212\u20091.28. ALT, \u03b3-GT, ALP, and total bilirubin decreased significantly at all pemafibrate doses vs. placebo, with the greatest decrease in the pemafibrate 0.4\u2009mg\/day group: LS mean change from baseline in ALT \u2212\u20097.6 U\/L; \u03b3-GT \u2212\u200937.3 U\/L; ALP \u2212\u200984.7 U\/L; and total bilirubin \u2212\u20092.27\u2009\u00b5mol\/L. Changes in HbA1c and AST did not differ significantly from placebo in any pemafibrate groups in the overall study population. The decreases from baseline in LFTs and glucose metabolism markers except for HbA1c were notable among patients with higher baseline values. FGF21 increased significantly in all pemafibrate groups compared to placebo, with the greatest increase in the pemafibrate 0.4\u2009mg\/day group. Adverse event rates were similar in all groups including placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In patients with hypertriglyceridemia, pemafibrate can improve glucose metabolism and liver function, and increase FGF21, without increasing adverse event risk.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12933-021-01291-w","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T05:27:25Z","timestamp":1620192445000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Effects of pemafibrate on glucose metabolism markers and liver function tests in patients with hypertriglyceridemia: a pooled analysis of six phase 2 and phase 3 randomized double\u2010blind placebo\u2010controlled clinical trials"],"prefix":"10.1186","volume":"20","author":[{"given":"Koutaro","family":"Yokote","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuya","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsunori","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Nojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Suganami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Ishibashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"issue":"5","key":"1291_CR1","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1007\/s00125-015-3525-8","volume":"58","author":"B Verg\u00e9s","year":"2015","unstructured":"Verg\u00e9s B. 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The sub-studies that constitute this study were approved by the institutional review boards at their respective study sites, and written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KY has received personal fees and grants from Kowa Company, Ltd., MSD K.K., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Pfizer Japan Inc., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., and Taisho Pharmaceutical Co., Ltd., personal fees from Amgen K.K., Sanofi K.K., AstraZeneca K.K., Novartis Pharma K.K., Kyowa Kirin Co., Ltd., and Janssen Pharmaceutical K.K., grants from Kao Corporation, Teijin Pharma Limited, Shionogi & Co., Ltd., and Bayer Yakuhin, Ltd, and holds an endowed chair funded by MSD K.K. SY has received personal fees and grants from MSD K.K., personal fees from Kowa Company, Ltd., Amgen K.K., and Sanofi K.K., and grants from Bayer Yakuhin, Ltd., Nippon Boehringer Ingelheim Co., Ltd., Takeda Pharmaceutical Company Limited, Ono Pharmaceutical Co., Ltd., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Hitachi Chemical Diagnostics Systems Co., Ltd., and Rohto Pharmaceutical Co., Ltd. HA has received personal fees from Sanofi K.K., Daiichi Sankyo Company, Limited, Astellas Pharma Inc., MSD K.K., Abbott Japan LLC, Kowa Company, Ltd., Amgen K.K., Pfizer Japan Inc., Takeda Pharmaceutical Company Limited, Otsuka Pharmaceutical Co., Ltd., and UCB Japan Co. Ltd. EA has received personal fees and grants from Kowa Company, Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., and Novo Nordisk Pharma Ltd., personal fees from AstraZeneca K.K., MSD K.K., and Ono Pharmaceutical Co., Ltd., grants from Astellas Pharma Inc., Daiichi Sankyo Company, Limited, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Bayer Yakuhin, Ltd., and Pfizer Japan Inc., and holds an endowed chair funded by MSD K.K., Ono Pharmaceutical Co., Ltd., and Terumo Corporation. MM, TN, and HS are employees of Kowa Company, Ltd. SI has received personal fees from Kowa Company, Ltd., and grants from Ono Pharmaceutical Co., Ltd.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"96"}}